Signaling via BCR (B-Cell Receptor) signaling is thought to play a role in the pathogenesis and/or progression of disease, e.g., chronic lymphocytic leukemia (CLL). Moreover, agents that target B-cell receptor (BCR) signaling in lymphoid and leukemia malignancies including ibrutinib and acalabrutinib (4-{8-Amino-3-[(2S)-1-(2-butynoyl)-2-pyrrolidinyl]imidazo[1,5-a]pyrazin-1-yl}-N-(2-pyridinyl)benzamide), which inhibit Bruton's tyrosine kinase (BTK), have shown significant clinical activity. By disrupting B-cell signaling pathways, BTK treatment has been associated with a dramatic lymph node response, but eradication of disease and relapse in high risk disease remain challenges.
Provided here are solutions to these and other problems in the art.